ENZYMATIC AND CHEMOENZYMATIC - SYNTHESIS AND STEREOCHEMICAL ASSIGNMENT OF CIS-DIHYDRODIOL DERIVATIVES OF MONOSUBSTITUTED BENZENES

Toluene dioxygenase-catalysed oxidation of mono-substituted benzene su bstrates (R = F, Cl, Br, I, Me, Et, CH2OAc, CH=CH2, C=H, CF3, CN, OMe, OEt, SMe) in growing cultures of Pseudomonas putida UV4 yielded the c orresponding cis-dihydrodiol metabolites. Palladium-catalysed cross-co upling of is-(1S,2S)-1,2-dihydroxy-3-iodocyclohexa-3,5-diene with a ra nge of tributyltin compounds provided a chemoenzymatic route to a furt her series of cis-dihydrodiol derivatives of monosubstituted benzenes (R = D, CH2CH=CH2, Bu-n, SEt, SPri, SBut, SPh, SC6H4Me-4). The enantio purities and absolute configurations of the cis-dihydrodiols, obtained by both enzymatic and chemoenzymatic routes, were determined by sever al new:methods including H-1 NMR spectroscopic analysis of the bis-MTP A esters of the 4-phenyl-1,2,4-triazoline-3,5-dione cycloadducts, X-ra y crystallography, circular dichroism spectroscopy and stereochemical correlation.